Soybean Sprout Peptides Alleviate Obesity via PI3K-Akt and JAK-STAT Pathway Modulation, Gut Microbiota Regulation, and Metabolic Reprogramming.

Obesity is a growing global health concern associated with severe metabolic disorders, necessitating the development of safer and more effective therapeutic strategies. Soybean sprout peptides (SSPs), derived from germinated soybeans, are bioactive compounds with potential antiobesity effects. This study aimed to investigate the molecular mechanisms of SSPs through an integrated approach combining network pharmacology, molecular docking, and in vivo experiments. SSP sequences were identified using UPLC-Orbitrap-MS/MS, and their bioactivity was predicted using PeptideRanker. Network pharmacology identified key SSP targets, including AKT1, SRC, STAT3, ESR1, FOS, and NFKB1, which are implicated in the PI3K-Akt and JAK-STAT pathways. Molecular docking validated strong interactions between SSPs and these targets. In vivo, SSP administration significantly reduced body weight gain, abdominal fat accumulation, and serum lipid abnormalities in high-fat-diet-induced obese mice while modulating gut microbiota composition by restoring the Firmicutes-to-Bacteroidetes ratio and reducing pathogenic taxa. Fecal metabolomics revealed that SSP alleviated oxidative stress and improved amino acid metabolism, contributing to its antiobesity effects. These findings suggest that SSP holds promise as a functional food ingredient or nutraceutical for obesity prevention and management.